The purpose of this project is to further define those disorders of peripheral blood phagocytic function that render the patient susceptible to serious bacterial infection. The emphasis will be on biochemical mechanisms involved in intracellular bacterial killing by normal and abnormal leukocytes. Abnormal leukocyte phagocytic and bactericidal function is already known for a group of leukocytes deficient in certain enzymes, i.e. chronic granulomatous disease leukocytes lacking DPNH oxidase, total deficiency of glucose-6-phosphate dehydrogenase (G6PD), myeloperoxidase deficiency, and phosphoglycerate kinase deficient leukocytes. All of these enzyme deficient leukocytes fail to iodinate and kill bacteria and fungi that require normal peroxidation by leukocytes. The specific aims of this project are (a) to define the enzymatic source(s) of hydrogen peroxide and the biochemical mechanisms in leukocytes that make it accessible for bacterial killing, (b) enzyme deficient leukocytes and inhibitors of key leukocyte enzymes involved in normal phagocytic function will be utilized to define the biochemical reactions needed for normal bacterial killing, (c) to characterize those physical factors such as surface contact by particles and bacteria that activate those oxidative biochemical reactions culminating in normal bacterial killing. In addition, biochemical, phagocytic, and bactericidal compensatory adaptive and regulatory mechanisms by the phagocyte exposed to a variety of host factors such as infection, major systemic disease, drug therapies, and malignancy will be investigated.